RESUMO
AIM: The aim of this study was to explore the mechanism underlying the protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-ß-D-glucoside (TSG) against osteoporosis. METHOD: MC3T3-E1 mouse osteoblast precursor cells were used to analyze the protective effects of TSG on osteoblast apoptosis and differential inhibition induced by oxidative stress to determine the gene expression of forkhead transcription factor FKHRL1 (FoxO3a), T cell factors (TCFs), and downstream genes. A mouse model was used to assess the protective effects of TSG on ovariectomy-induced osteoporosis as well as on Cell Counting Kit-8 (CCK) gene expression, including that of FoxO3a. The mechanism underlying the protective effects of TSG against osteoporosis was further explored using high-throughput sequencing data. RESULTS: A CCK-8 assay in MC3T3-E1 cells and hematoxylin and eosin staining in mouse tissue indicated that cell viability and bone tissue development were inhibited by oxidative stress and ovariectomy and that TSG neutralized or attenuated this effect. The expression levels of FoxO3a, TCF, and downstream genes and the indices of oxidative stress were the same in MC3T3-E1 cells and the bone tissues of the mouse model. Bioinformatics analysis indicated that the cardiac muscle contraction and chemokine signaling pathway were disturbed in MC3T3-E1 cells treated with hydrogen peroxide. Gene ontology-biological process analysis revealed the influence of TSG treatment. CONCLUSION: Osteoporosis and cardiac diseases appear to share a common mechanism. In addition to Wnt/FoxO3a signaling, the immune system and the chemokine signaling pathway may contribute to the protective mechanism of TSG.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Glucosídeos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Estilbenos/farmacologia , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Quimiocinas/metabolismo , Modelos Animais de Doenças , Feminino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Fatores de Transcrição TCF/genética , Fatores de Transcrição TCF/metabolismo , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
One of the most fascinating findings in retrovirology is the construction of viral vectors based on foamy viruses (FVs) for gene therapy. The envelope glycoprotein (Env), one of the structural proteins of FV, is an important antigen in the immunoassays, as it is highly specific. To compare the characteristics of all 15 available FV Envs, the phylogenesis, hydrophobicity, modifications, and conserved motifs were analyzed based on the Env sequences. Meanwhile, the secondary structures of transmembrane (TM) domains of FV Envs were predicted. The results of phylogenetic analyses based on Envs indicated that the foamy viruses from different hosts could form three groups. The hydrophobicity analysis revealed that FV Envs had two prominent hydrophobic regions, which was similar to other retroviruses. Though the glycosylation, ubiquitination, and the secondary structures of TM domains of FV Envs were in line with other retroviruses, the roles were distinctly different. Interestingly, the analyses of conserved motifs suggested that FV Envs possessed several specific functional motifs.
